Myocardial protection during heart surgery by IGF-1 and bcl-2 gene introduction.

通过引入 IGF-1 和 bcl-2 基因来保护心脏手术期间的心肌。

• 批准号: 10671275
• 负责人: OTANI Hajime
• 金额: $ 1.6万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671275/
• 关键词: myocardial ischemia; IGF-1; Bcl-xL; Bax; Bcl-2; IGF-I

Insulin like growth factor-1 (IGF-1) has become a promising tool for treatment with end-stage heart failure. Although the underlying mechanism for myocardial protection remains elusive, recent studies suggest that altered regulation of Bcl-2 family proteins may be involved in the cytoprotective action of IGF-1. It has also been clear that intracellular localization of Bcl-2 family proteins is crucial in regulating the release of death-promoting cytochrome c from mitochondria. Therefore, we have investigated the effect of IGF-1 on Bcl-2 family protein expression and cytochrome c release in isolated rat heart mitochondria. Rats were treated with intra-peritoneal injection with IGF-1(3mg/kg). Mitochondria were isolated from the heart 12, 24, and 36 hours after the treatment. Western blot analysis showed that Bcl-xL expression was maximally increased in the rat heart mitochondria 24 hours after IGF-1 treatment, while Bax expression was maximally down-regulated in the same mitochondrial fra … More ction. Neither Bcl-xL nor Bax protein was detected in the cytosol fraction at any time point after IGF-1treatment. Bcl-2 protein was undetectable in mitochondria, cytosol, microsome or nuclearmyofibrillar fraction. Immunohistochemical staining revealed that IGF-1-induced overexpression of Bcl-xL in the heart was confined to cardiomyocytes. Isolated rat heart mitochondria did not release cytochrome c without a respiratory substrate succinate even in the presence of 10μM CaィイD12+ィエD1. However, respiring mitochondria released cytochrome c in a CaィイD12+ィエD1 dependent manner. Cytochrome c release was attenuated in mitochondria obtained from the heart treated with IGF-1. These results suggest that IGF-1 differentially regulates expression of Bcl-xL and Bax proteins in the rat heart mitochondria. IGF-1-Induced inhibition of cytochrome c release from the mitochondria may represent a mechanism for inhibition of apoptotic cardimyocyte cell death in patients with end-stage heart failure, or with reperfusion injury. Less

胰岛素样生长因子-1（IGF-1）已成为治疗终末期心力衰竭的一种有前途的工具。虽然心肌保护的潜在机制仍然难以捉摸，但最近的研究表明，Bcl-2家族蛋白的调节改变可能参与IGF-1的细胞保护作用。同样清楚的是，Bcl-2家族蛋白的细胞内定位在调节线粒体释放促死亡细胞色素c中是至关重要的。因此，我们研究了IGF-1对Bcl-2家族蛋白表达和细胞色素c释放在离体大鼠心脏线粒体的影响。腹腔注射IGF-1（3 mg/kg）。在处理后12、24和36小时从心脏分离线粒体。Western blot分析显示，IGF-1处理后24小时，Bcl-xL在大鼠心肌线粒体中的表达最高，而Bax在同一线粒体中的表达最低。 ...更多信息 - 是的在IGF-1处理后的任何时间点，胞浆中均未检测到Bcl-xL和Bax蛋白。Bcl-2蛋白在线粒体、细胞质、微粒体和核肌原纤维中均未检测到。免疫组织化学染色显示，IGF-1诱导的Bcl-xL在心脏中的过度表达仅限于心肌细胞。即使在10μM Ca ~（2+）D_12 + Ca ~（2+）D_1存在下，离体大鼠心脏线粒体在没有呼吸底物琥珀酸的情况下也不释放细胞色素c。然而，呼吸线粒体释放细胞色素c在Ca ~（2+）D_12 + Ca ~（2+）D_1依赖的方式。细胞色素c的释放在从IGF-1处理的心脏获得的线粒体中减弱。这些结果表明，IGF-1差异调节大鼠心脏线粒体中Bcl-xL和Bax蛋白的表达。IGF-1诱导的细胞色素c从线粒体释放的抑制可能代表了终末期心力衰竭或再灌注损伤患者心肌细胞凋亡的抑制机制。少

项目成果

Otani,H et. al: "Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a Wortmannin-sensitive mechanism"JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. 35:(2). 275-281 (2000)

大谷，H 等。

Otani, H et al.: "Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a Wortmannin-sensitive mechanism"JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. 35 : (2). 275-281 (2000)

Otani, H 等人：“胰岛素样生长因子-I 通过渥曼青霉素敏感机制改善离体大鼠心脏再灌注期间心脏功能的恢复”心血管药理学杂志。